Effect of Supplementation with Omega-3 Polyunsaturated Fatty Acids on Metabolic Modulators in Skeletal Muscle of Rats with an Obesogenic High-Fat Diet.

Previous studies provided evidence of the benefits of omega-3 polyunsaturated fatty acids (ω-3 PUFA) on the cardiovascular system and inflammation. However, its possible effect on skeletal muscle is unknown. This study aimed to evaluate whether ω-3 PUFA reverses the dysregulation of metabolic modulators in the skeletal muscle of rats on a high-fat obesogenic diet. For this purpose, an animal model was developed using male Wistar rats with a high-fat diet (HFD) and subsequently supplemented with ω-3 PUFA. Insulin resistance was assessed, and gene and protein expression of metabolism modulators in skeletal muscle was also calculated using PCR-RT and Western blot. Our results confirmed that in HFD rats, zoometric parameters and insulin resistance were increased compared to SD rats. Furthermore, we demonstrate reduced gene and protein expression of peroxisome proliferator-activated receptors (PPARs) and insulin signaling molecules. After ω-3 PUFA supplementation, we observed that glucose (24.34%), triglycerides (35.78%), and HOMA-IR (40.10%) were reduced, and QUICKI (12.16%) increased compared to HFD rats. Furthermore, in skeletal muscle, we detected increased gene and protein expression of PPAR-α, PPAR-γ, insulin receptor (INSR), insulin receptor substrate 1 (ISR-1), phosphatidylinositol-3-kinase (PI3K), and glucose transporter 4 (GLUT-4). These findings suggest that ω-3 PUFAs decrease insulin resistance of obese skeletal muscle.

The efficacy of Omega-3 polyunsaturated fatty acids for severe burn patients: A systematic review and trial sequential meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: Severe burns lead to metabolic changes, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Omege-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties. In the absence of substantial evidence for use on major burns, we systematically reviewed the efficacy of omega-3 PUFAs for patients with severe burns. METHODS: We comprehensively searched MEDLINE, Web of Science, Embase, Cochrane Library, China National Knowledge Internet, Wang Fang Data, Chinese Biomedicine Database, and Science Direct databases to collect randomised controlled trials of omega-3 PUFAs administered to patients with burns from January 2000 to June 2023. Two researchers independently screened the literatures, extracted the data, and assessed the risk of bias in the included studies. The outcomes were mortality, the risk of severe sepsis, septic shock, and multiple organ dysfunction syndrome. Data synthesis was conducted using Review Manager. Trial sequential analyses (TSA) for outcomes were performed. RESULTS: Three randomised controlled trials involving 140 patients were included. Of these, 71 patients received omega-3 PUFAs. The results showed that omega-3 PUFAs significantly reduced the incidence of severe sepsis, septic shock, multiple organ dysfunction syndrome (RR = 0.38, 95 % CI [0.19, 0.75], P = 0.005), C-reactive protein levels (MD = -39.70[-81.63, 2.23], P = 0.06), and improved respiratory outcomes. However, there was no difference in 14-day mortality (RR = 1.10, 95%CI [0.59, 2.05], P = 0.75). TSA showed that the results for the incidence of severe sepsis, septic shock, multiple organ dysfunction syndrome are insufficient and inconclusive. CONCLUSIONS: Omega-3 PUFAs may reduce inflammatory response and risk of sepsis, septic shock, and multiple organ dysfunction syndrome in severe burns patients and may shorten hospital stay but cannot reduce risk of death. Due to the limitation of the quantity and quality of the included studies, the evidence level is low, and the conclusions need to be verified by larger scale and higher quality randomised controlled trials.

Omega-3 supplementation improves depressive symptoms, cognitive function and niacin skin flushing response in adolescent depression: A randomized controlled clinical trial.

BACKGROUND: Depressive disorder in adolescents is a major health problem with inadequate treatment. Omega-3 (ω3) polyunsaturated fatty acids are a promising adjuvant therapy in adult depression. The primary objective of this study was to investigate the efficacy of adjuvant ω3 treatment on depressive symptoms in adolescent depression. Secondarily, we explored the effects of ω3 on cognitive function and memory and niacin skin flushing response (NSFR), as their robust associations with adolescent depression. METHODS: A total of 71 adolescents with depression (aged 13-24; 59.2 % female) were randomly assigned to receive ω3 plus Paxil (n = 34) or Paxil alone (n = 37) for 12 weeks. Primary outcome was depression severity according to scores on Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes were cognitive function and memory, and NSFR. RESULTS: Significant improvements in depressive symptoms over time (p = 0.00027 at week 12) were observed in the ω3 + Paxil group compared with Paxil group. Additionally, in the ω3 + Paxil group, significant improvements in memory over time, and greater cognitive function and NSFR were also observed compared with the Paxil group; the NSFR was negatively correlated with MADRS scores at baseline. LIMITATIONS: The trial was open label; thus, the outcome measures should be viewed as preliminary since inherent bias in outcomes due to the potential of a placebo effect. CONCLUSIONS: Our results demonstrate that adjuvant ω3 treatment is effective for reducing depressive symptoms as well as improving cognitive function, memory and the NSFR; these results suggest ω3 is a promising adjuvant treatment for adolescent depression.

Omega-3 polyunsaturated fatty acids protect peritoneal mesothelial cells from hyperglycolysis and mesothelial-mesenchymal transition through the FFAR4/CaMKKß/AMPK/mTOR signaling pathway.

Peritoneal fibrosis is a severe clinical complication associated with peritoneal dialysis (PD) and impacts its efficacy and patient outcomes. The process of mesothelial-mesenchymal transition (MMT) in peritoneal mesothelial cells plays a pivotal role in fibrogenesis, whereas metabolic reprogramming, characterized by excessive glycolysis, is essential in MMT development. No reliable therapies are available despite substantial progress made in understanding the mechanisms underlying peritoneal fibrosis. Protective effect of omega-3 polyunsaturated fatty acids (ω3 PUFAs) has been described in PD-induced peritoneal fibrosis, although the detailed mechanisms remain unknown. It is known that ω3 PUFAs bind to and activate the free fatty acid receptor 4 (FFAR4). However, the expression and role of FFAR4 in the peritoneum have not been investigated. Thus, we hypothesized that ω3 PUFAs would alleviate peritoneal fibrosis by inhibiting hyperglycolysis and MMT through FFAR4 activation. First, we determined FFAR4 expression in peritoneal mesothelium in humans and mice. FFAR4 expression was abnormally decreased in patients on PD and mice and HMrSV5 mesothelial cells exposed to PD fluid (PDF); this change was restored by the ω3 PUFAs (EPA and DHA). ω3 PUFAs significantly inhibited peritoneal hyperglycolysis, MMT, and fibrosis in PDF-treated mice and HMrSV5 mesothelial cells; these changes induced by ω3 PUFAs were blunted by treatment with the FFAR4 antagonist AH7614 and FFAR4 siRNA. Additionally, ω3 PUFAs induced FFAR4, Ca2+/calmodulin-dependent protein kinase kinase ß (CaMKKß), and AMPK and suppressed mTOR, leading to the inhibition of hyperglycolysis, demonstrating that the ω3 PUFAs-mediated FFAR4 activation ameliorated peritoneal fibrosis by inhibiting hyperglycolysis and MMT via CaMKKß/AMPK/mTOR signaling. As natural FFAR4 agonists, ω3 PUFAs may be considered for the treatment of PD-associated peritoneal fibrosis.

Omega-3 polyunsaturated fatty acids supplementation improves memory in first-diagnosed, drug-naïve patients with depression: Secondary analysis of data from a randomized controlled trial.

INTRODUCTION: Cognitive impairments are found in most patients with major depressive disorder (MDD). It is believed that low Omega-3 polyunsaturated fatty acids (n-3 PUFAs) level raise the risk of anxiety, depressive symptoms and cognition dysfunction. Since our previous research has found n-3 PUFAs supplementation improves anxiety in MDD, this study was to further explore the effectiveness on cognitive impairment among depressed patients. METHODS: A total of 72 venlafaxine treated outpatients with first-diagnosed, drug-naïve depression were enrolled. Daily n-3 PUFAs supplementation (2.4 g/d of fish oil, including 1440 mg eicosapentaenoic acid and 960 mg of docosahexaenoic acid) or placebo was used for 12 weeks. Cognitive function, measure by repeatable battery for the assessment of neuropsychological status ([RBANS]) scores, was compared over time. RESULTS: Immediate memory, delayed memory and RBANS total scores were significant higher in both groups at week 4 and week 12 compared with baseline. Both groups exhibited improvement on attention scores at week 12. No significant differences were observed comparing n-3 PUFAs with placebo groups in the improvement of total RBANS scores and other subscales except in the change of immediate memory at both week 4 and week 12 (p < 0.05). LIMITATIONS: Sample size was relatively low. Moreover, multiple ethnic populations and the income of patients should be considered. Lastly, we used raw scores instead of the standardized scores of RBANS. CONCLUSION: N-3 PUFAs supplementation yielded a small but statistically significant improvement on immediate memory in first-diagnosed, drug-naïve depressed patients. While, antidepressant treatment resulted in significant improvement of cognitive function.

Nutrition as the foundation for successful aging: a focus on dietary protein and omega-3 polyunsaturated fatty acids.

Skeletal muscle plays a critical role throughout the aging process. People living with sarcopenia, a progressive and generalized loss of skeletal muscle mass and function, often experience diminished quality of life, which can be attributed to a long period of decline and disability. Therefore, it is important to identify modifiable factors that preserve skeletal muscle and promote successful aging (SA). In this review, SA was defined as (1) low cardiometabolic risk, (2) preservation of physical function, and (3) positive state of wellbeing, with nutrition as an integral component. Several studies identify nutrition, specifically high-quality protein (eg, containing all essential amino acids), and long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), as positive regulators of SA. Recently, an additive anabolic effect of protein and n-3 PUFAs has been identified in skeletal muscle of older adults. Evidence further suggests that the additive effect of protein and n-3 PUFAs may project beyond skeletal muscle anabolism and promote SA. The key mechanism(s) behind the enhanced effects of intake of protein and n-3 PUFAs needs to be defined. The first objective of this review is to evaluate skeletal muscle as a driver of cardiometabolic health, physical function, and wellbeing to promote SA. The second objective is to examine observational and interventional evidence of protein and n-3 PUFAs on skeletal muscle to promote SA. The final objective is to propose mechanisms by which combined optimal intake of high-quality protein and n-3 PUFAs likely play a key role in SA. Current evidence suggests that increased intake of protein above the Recommended Dietary Allowance and n-3 PUFAs above the Dietary Guidelines for Americans recommendations for late middle-aged and older adults is required to maintain skeletal muscle mass and to promote SA, potentially through the mechanistical target of rapamycin complex 1 (mTORC1).

Omega-3 polyunsaturated fatty acids in the prevention of relapse in patients with stable bipolar disorder: A 6-month pilot randomized controlled trial.

This study investigated the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in relapse prevention of bipolar disorder (BD), addressing the shortcomings of current medications. Thirty-one stable BD patients were randomized to receive n-3 PUFAs or placebo for 6 months and intergroup differences in the incidence of the recurrence of bipolar depression were assessed. Differences in depression severity, manic symptoms, and routine biochemical parameters were also assessed. Interestingly, n-3 PUFAs demonstrated a favorable preventive effect on bipolar depression recurrence (p=0.005; Log-Rank) and reduced depression severity compared to placebo, and were well-tolerated, suggesting their potential as a safe prophylactic therapy for BD.

Omega-3 fatty acid supply in pregnancy for risk reduction of preterm and early preterm birth.

This clinical practice guideline on the supply of the omega-3 docosahexaenoic acid and eicosapentaenoic acid in pregnant women for risk reduction of preterm birth and early preterm birth was developed with support from several medical-scientific organizations, and is based on a review of the available strong evidence from randomized clinical trials and a formal consensus process. We concluded the following. Women of childbearing age should obtain a supply of at least 250 mg/d of docosahexaenoic+eicosapentaenoic acid from diet or supplements, and in pregnancy an additional intake of ≥100 to 200 mg/d of docosahexaenoic acid. Pregnant women with a low docosahexaenoic acid intake and/or low docosahexaenoic acid blood levels have an increased risk of preterm birth and early preterm birth. Thus, they should receive a supply of approximately 600 to 1000 mg/d of docosahexaenoic+eicosapentaenoic acid, or docosahexaenoic acid alone, given that this dosage showed significant reduction of preterm birth and early preterm birth in randomized controlled trials. This additional supply should preferably begin in the second trimester of pregnancy (not later than approximately 20 weeks' gestation) and continue until approximately 37 weeks' gestation or until childbirth if before 37 weeks' gestation. Identification of women with inadequate omega-3 supply is achievable by a set of standardized questions on intake. Docosahexaenoic acid measurement from blood is another option to identify women with low status, but further standardization of laboratory methods and appropriate cutoff values is needed. Information on how to achieve an appropriate intake of docosahexaenoic acid or docosahexaenoic+eicosapentaenoic acid for women of childbearing age and pregnant women should be provided to women and their partners.

Fish consumption and omega-3 polyunsaturated fatty acids from diet are positively associated with cognitive function in older adults even in the presence of exposure to lead, cadmium, selenium, and methylmercury: a cross-sectional study using NHANES 2011-2014 data.

BACKGROUND: Long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are reported to be beneficial for cognition, but limited consumption of some fish is recommended due to high concentrations of heavy metals and persistent organics. OBJECTIVE: We aimed to determine whether dietary ω-3 PUFAs from fish consumption are associated with higher cognitive scores in older adults and explored the associations of mixtures of ω-3 PUFAs and blood concentrations of lead, cadmium, selenium, and methylmercury on cognitive performance. METHODS: We conducted a cross-sectional study with data from the NHANES 2011-2014, assessing cognitive scores of immediate recall, delayed recall, and executive function in adults ≥60 y (n = 3123). We performed multivariate linear regressions and mixture models utilizing the quantile-based g-computation method to identify associations between monthly fish consumption or dietary ω-3 PUFAs with blood concentrations of lead, cadmium, methyl mercury, and selenium on cognitive scores. RESULTS: Fish consumption had significant positive associations with all 3 cognitive scores, whereas dietary ω-3 PUFAs were only significantly associated with the Digit Symbol Substitution Test (DSST) scores. Mixture analysis showed significant positive associations with DSST scores for fish consumption (ß: 0.88; 95% CI: 0.48, 1.29) and dietary ω-3 PUFAs (ß: 0.41; 95% CI: 0.03, 0.78) with positive component weights for fish consumption, dietary ω-3 PUFAs, and blood selenium and negative component weight for blood cadmium concentrations. CONCLUSIONS: Our findings support dietary recommendations for older adults to consume fish to maintain cognitive function, likely due to biomolecular actions of ω-3 PUFAs that increase neuronal membrane fluidity, have antioxidation activity, and restore cell damage. The combination of selenium and fish consumption or ω-3 PUFAs was associated with reduced decline in cognitive scores and less negative associations from exposures to lead, cadmium, and mercury compounds.

Unraveling the impact of Omega-3 polyunsaturated fatty acids on blood-brain barrier (BBB) integrity and glymphatic function.

Alzheimer's disease (AD) and other forms of dementia represent major public health challenges but effective therapeutic options are limited. Pathological brain aging is associated with microvascular changes and impaired clearance systems. The application of omega-3 polyunsaturated fatty acids (n-3 or omega-3 PUFAs) is one of the most promising nutritional interventions in neurodegenerative disorders from epidemiological data, clinical and pre-clinical studies. As essential components of neuronal membranes, n-3 PUFAs have shown neuroprotection and anti-inflammatory effects, as well as modulatory effects through microvascular pathophysiology, amyloid-beta (Aß) clearance and glymphatic pathways. This review meticulously explores these underlying mechanisms that contribute to the beneficial effects of n-3 PUFAs against AD and dementia, synthesizing evidence from both animal and interventional studies.

Cardiovascular Diseases and Marine Oils: A Focus on Omega-3 Polyunsaturated Fatty Acids and Polar Lipids.

Cardiovascular diseases (CVD) remain the leading cause of death across the globe, hence, establishing strategies to counteract CVD are imperative to reduce mortality and the burden on health systems. Dietary modification is an effective primary prevention strategy against CVD. Research regarding dietary supplementation has become increasingly popular. This review focuses on the current in vivo, in vitro, and epidemiological studies associated with that of omega-3 polyunsaturated fatty acids (n-3 PUFAs) and polar lipids (PLs) and how they play a role against CVD. Furthermore, this review focuses on the results of several major clinical trials examining n-3 PUFAs regarding both primary and secondary prevention of CVD. Notably, we place a lens on the REDUCE-IT and STRENGTH trials. Finally, supplementation of PLs has recently been suggested as a potential alternative avenue for the reduction of CVD incidence versus neutral forms of n-3 PUFAs. However, the clinical evidence for this argument is currently rather limited. Therefore, we draw on the current literature to suggest future clinical trials for PL supplementation. We conclude that despite conflicting evidence, future human trials must be completed to confirm whether PL supplementation may be more effective than n-3 PUFA supplementation to reduce cardiovascular risk.

Evaluating the Effects of Omega-3 Polyunsaturated Fatty Acids on Inflammatory Bowel Disease via Circulating Metabolites: A Mediation Mendelian Randomization Study.

Epidemiological evidence regarding the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on inflammatory bowel disease (IBD) is conflicting. Additionally, little evidence exists regarding the effects of specific omega-3 components on IBD risk. We applied two-sample Mendelian randomization (MR) to disentangle the effects of omega-3 PUFAs (including total omega-3, α-linolenic acid, eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA)) on the risk of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Our findings indicated that genetically predicted increased EPA concentrations were associated with decreased risk of IBD (odds ratio 0.78 (95% CI 0.63-0.98)). This effect was found to be mediated through lower levels of linoleic acid and histidine metabolites. However, we found limited evidence to support the effects of total omega-3, α-linolenic acid, and DHA on the risks of IBD. In the fatty acid desaturase 2 (FADS2) region, robust colocalization evidence was observed, suggesting the primary role of the FADS2 gene in mediating the effects of omega-3 PUFAs on IBD. Therefore, the present MR study highlights EPA as the predominant active component of omega-3 fatty acids in relation to decreased risk of IBD, potentially via its interaction with linoleic acid and histidine metabolites. Additionally, the FADS2 gene likely mediates the effects of omega-3 PUFAs on IBD risk.

Roles of Omega-3 Polyunsaturated Fatty Acids in Managing Cognitive Impairment in Chronic Obstructive Pulmonary Disease: A Review.

Chronic obstructive pulmonary disease (COPD) contributes significantly to the death of people worldwide, especially the elderly. An essential feature of COPD is pulmonary inflammation, which results from long-term exposure to noxious substances from cigarette smoking and other environmental pollutants. Pulmonary inflammatory mediators spill over to the blood, leading to systemic inflammation, which is believed to play a significant role in the onset of a host of comorbidities associated with COPD. A substantial comorbidity of concern in COPD patients that is often overlooked in COPD management is cognitive impairment. The exact pathophysiology of cognitive impairment in COPD patients remains a mystery; however, hypoxia, oxidative stress, systemic inflammation, and cerebral manifestations of these conditions are believed to play crucial roles. Furthermore, the use of medications to treat cognitive impairment symptomatology in COPD patients has been reported to be associated with life-threatening adverse effects, hence the need for alternative medications with reduced side effects. In this Review, we aim to discuss the impact of cognitive impairment in COPD management and the potential mechanisms associated with increased risk of cognitive impairment in COPD patients. The promising roles of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in improving cognitive deficits in COPD patients are also discussed. Interestingly, ω-3 PUFAs can potentially enhance the cognitive impairment symptomatology associated with COPD because they can modulate inflammatory processes, activate the antioxidant defence system, and promote amyloid-beta clearance from the brain. Thus, clinical studies are crucial to assess the efficacy of ω-3 PUFAs in managing cognitive impairment in COPD patients.

A review of recent studies on the enrichment of eggs and poultry meat with omega-3 polyunsaturated fatty acids: novel findings and unanswered questions.

Studies from our laboratory over the past decade have yielded new information with regard to the dietary enrichment of eggs and poultry meat with omega-3 (n-3) polyunsaturated fatty acids (PUFA) but have also generated a number of unanswered questions. In this review, we summarize the novel findings from this work, identify knowledge gaps, and offer possible explanations for some perplexing observations. Specifically discussed are: 1) Why feeding laying hens and broilers an oil rich in stearidonic acid (SDA; 18:4 n-3), which theoretically bypasses the putative rate-limiting step in the hepatic n-3 PUFA biosynthetic pathway, does not enrich egg yolks and tissues with very long-chain (VLC; ≥20 C) n-3 PUFA to the same degree as obtained by feeding birds oils rich in preformed VLC n-3 PUFA; 2) Why in hens fed an SDA-rich oil, SDA fails to accumulate in egg yolk but is readily incorporated into adipose tissue; 3) How oils rich in oleic acid (OA; 18:1 n-9), when co-fed with various sources of n-3 PUFA, attenuates egg and tissue n-3 PUFA contents or rescues egg production when co-fed with a level of docosahexaenoic acid (DHA; 22:6 n-3) that causes severe hypotriglyceridemia; and 4) Why the efficiency of VLC n-3 PUFA deposition into eggs and poultry meat is inversely related to the dietary content of α-linolenic acid (ALA; 18:3 n-3), SDA, or DHA.

Omega-3 Polyunsaturated Fatty Acids and Their Anti-Oxidant, Anti-Inflammatory and Neuroprotective Effects in Diabetic Retinopathy: A Narrative Review.

Diabetic retinopathy (DR) is a common microvascular complication of type 2 Diabetes Mellitus (T2DM) that can have vision-threatening consequences, particularly if it advances to the proliferative stage and is left untreated. Owing to the central role of hyperglycemia-induced oxidative stress, multiple anti-oxidants have been investigated for their therapeutic value. However, there is a lack of substantial data to support the use of any of the compounds tested so far. Omega-3 polyunsaturated fatty acids (PUFAs), namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have received much acclaim for their positive impact on cardiovascular health outcomes. The anti-oxidative, anti-inflammatory and neuroprotective properties of PUFAs also make them promising therapeutic and preventive agents for DR. The current evidence is derived mainly from in vitro and animal studies and provides some insight into the underlying mechanisms involved. These fatty acids are capable of direct anti-oxidative and anti-inflammatory effects. They also concomitantly promote intrinsic defense mechanisms and recovery, particularly of photoreceptor neurons. Hence, dietary supplementation with PUFAs, mainly from marine sources, can halt and reverse the retinal damage seen in DR. Furthermore, clinical trials have reported improved vision and quality of life in DR patients after supplementation. However, a major limitation of these trials is the use of nutraceutical formulations in which omega-3 PUFAs are combined with other anti-oxidant compounds, thereby preventing the evaluation of omega-3 as standalone treatment. Although the results of experimental studies to date have been promising, more clinical trials are required to determine the full extent of benefits in patients with DR.

Omega-3 Fatty Acids in Arterial Hypertension: Is There Any Good News?

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), including alpha-linolenic acid (ALA) and its derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are "essential" fatty acids mainly obtained from diet sources comprising plant oils, marine blue fish, and commercially available fish oil supplements. Many epidemiological and retrospective studies suggested that ω-3 PUFA consumption decreases the risk of cardiovascular disease, but results of early intervention trials have not consistently confirmed this effect. In recent years, some large-scale randomized controlled trials have shed new light on the potential role of ω-3 PUFAs, particularly high-dose EPA-only formulations, in cardiovascular prevention, making them an attractive tool for the treatment of "residual" cardiovascular risk. ω-3 PUFAs' beneficial effects on cardiovascular outcomes go far beyond the reduction in triglyceride levels and are thought to be mediated by their broadly documented "pleiotropic" actions, most of which are directed to vascular protection. A considerable number of clinical studies and meta-analyses suggest the beneficial effects of ω-3 PUFAs in the regulation of blood pressure in hypertensive and normotensive subjects. These effects occur mostly through regulation of the vascular tone that could be mediated by both endothelium-dependent and independent mechanisms. In this narrative review, we summarize the results of both experimental and clinical studies that evaluated the effect of ω-3 PUFAs on blood pressure, highlighting the mechanisms of their action on the vascular system and their possible impact on hypertension, hypertension-related vascular damage, and, ultimately, cardiovascular outcomes.

Development and internal validation of a non-invasive clinical tool to predict sufficient omega-3 levels in early pregnancy.

BACKGROUND: Complications from preterm birth (PTB) are the leading cause of death and disability in those under five years. Whilst the role of omega-3 (n-3) supplementation in reducing PTB is well-established, growing evidence suggests supplementation use in those replete may increase the risk of early PTB. AIM: To develop a non-invasive tool to identify individuals with total n-3 serum levels above 4.3% of total fatty acids in early pregnancy. METHODS: We conducted a prospective observational study recruiting 331 participants from three clinical sites in Newcastle, Australia. Eligible participants (n = 307) had a singleton pregnancy between 8 and 20 weeks' gestation at recruitment. Data on factors associated with n-3 serum levels were collected using an electronic questionnaire; these included estimated intake of n-3 (including food type, portion size, frequency of consumption), n-3 supplementation, and sociodemographic factors. The optimal cut-point of estimated n-3 intake that predicted mothers with total serum n-3 levels likely above 4.3% was developed using multivariate logistic regression, adjusting for maternal age, body mass index, socioeconomic status, and n-3 supplementation use. Total serum n-3 levels above 4.3% was selected as previous research has demonstrated that mothers with these levels are at increased risk of early PTB if they take additional n-3 supplementation during pregnancy. Models were evaluated using various performance metrics including sensitivity, specificity, area under receiver operator characteristic (AUROC) curve, true positive rate (TPR) at 10% false positive rate (FPR), Youden Index, Closest to (0,1) Criteria, Concordance Probability, and Index of Union. Internal validation was performed using 1000-bootstraps to generate 95% confidence intervals for performance metrics generated. RESULTS: Of 307 eligible participants included for analysis, 58.6% had total n-3 serum levels above 4.3%. The optimal model had a moderate discriminative ability (AUROC 0.744, 95% CI 0.742-0.746) with 84.7% sensitivity, 54.7% specificity and 37.6% TPR at 10% FPR. CONCLUSIONS: Our non-invasive tool was a moderate predictor of pregnant women with total serum n-3 levels above 4.3%; however, its performance is not yet adequate for clinical use. TRIAL REGISTRATION: This trial was approved by the Hunter New England Human Research Ethics Committee of the Hunter New England Local Health District (Reference 2020/ETH00498 on 07/05/2020 and 2020/ETH02881 on 08/12/2020).

Efficacy and safety of Omega-3 polyunsaturated fatty acids in adjuvant treatments for colorectal cancer: A meta-analysis of randomized controlled trials.

Background: Colorectal cancer (CRC) ranks third globally. There are many adverse reactions to treatments such as surgeries and post-surgical chemotherapy, which affect patients' prognosis and reduce their life quality. Omega-3 polyunsaturated fatty acids (O3FAs) have become an essential part of immune nutrition due to their anti-inflammatory properties, which improve body immunity and have attracted widespread attention. A systematic review focused on the efficacy and safety of O3FAs for patients undergoing surgeries in combination with chemotherapy or a surgery alone is lacking. Objectives: To evaluate the efficacy of O3FAs in the adjuvant treatment of CRC, a meta-analysis was conducted on patients with CRC who underwent surgeries in combination with chemotherapy or a surgery alone. Methods: As of March 2023, publications have been obtained using search terms from digital databases such as PubMed, Web of Science, Embase and Cochrane Library. Only randomized clinical trials (RCTs) evaluating the efficacy and safety of O3FAs following adjuvant treatments for CRC were included in the meta-analysis. Key outcomes were tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1beta (IL-1ß), albumin, body mass index (BMI), weight, the rate of infectious and non-infectious complications, the length of hospital stay (LOS), CRC mortality and life quality. Results: After screening 1,080 studies, 19 RCTs (n = 1,556) with O3FAs in CRC were included, in all of which at least one efficacy or safety outcome was examined. Compared to the control group, the level of TNF-α (MD = -0.79, 95% CI: 1.51 to -0.07, p = 0.03) and IL-6 was reduced due to O3FA-enriched nutrition during the perioperative period (MD = -4.70, 95% CI: 6.59 to -2.80, p < 0.00001). It also reduces LOS (MD = 9.36, 95% CI: 2.16 to 16.57, p = 0.01). No significant differences were found in CRP, IL-1ß, albumin, BMI, weight, the rate of infectious and non-infectious complications, CRC mortality or life quality. The inflammatory status of patients with CRC undergoing adjuvant therapies decreased after a total parenteral nutrition (TPN) O3FA supplementation (TNF-α, MD = -1.26, 95% CI: 2.25 to -0.27, p = 0.01, I 2 = 4%, n = 183 participants). The rate of infectious and non-infectious complications was reduced among patients with CRC undergoing adjuvant therapies after a parenteral nutrition (PN) O3FA supplementation (RR = 3.73, 95% CI: 1.52 to 9.17, p = 0.004, I 2 = 0%, n = 76 participants). Conclusion: Our observations suggest that supplementation with O3FAs has little or no effect on patients with CRC undergoing adjuvant therapies and that a prolonged inflammatory state may be modified. To validate these findings, well-designed, large-scale, randomized and controlled studies on homogeneous patient populations are expected.

Effect of omega-3 polyunsaturated fatty acids supplementation for patients with osteoarthritis: a meta-analysis.

BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) confers anti-inflammatory efficacy, which has been suggested to be effective for patients with osteoarthritis (OA). However, previous studies evaluating the influence of n-3 PUFAs supplementation in patients with OA showed inconsistent results. We performed a systematic review and meta-analysis to comprehensively evaluate the influence of n-3 PUFAs on symptom and joint function of patients with OA. METHODS: Relevant randomized controlled trials (RCTs) were obtained by searching PubMed, Embase, and Cochrane Library databases. A random-effects model was employed to combine the results. RESULTS: Nine RCTs with 2070 patients with OA contributed to the meta-analysis. Pooled results showed that n-3 PUFAs supplementation could significantly relieve the arthritis pain as compared to placebo (standardized mean difference [SMD]: - 0.29, 95% confidence interval [CI] - 0.47 to - 0.11, p = 0.002, I2 = 60%). Besides, supplementation with n-3 PUFAs was also associated with improved joint function (SMD: - 0.21, 95% CI - 0.34 to - 0.07, p = 0.002, I2 = 27%). Subgroup analysis showed consistent results of studies with arthritis pain and joint function evaluated by the Western Ontario-McMaster University Osteoarthritis Index and other scales (p for subgroup difference = 0.33 and 0.34, respectively). No severe treatment-related adverse events (AEs) were observed in the included patients, and the incidence of overall AEs was similar between groups (odds ratio: 0.97, 95% CI 0.64-1.45, p = 0.86, I2 = 0%). CONCLUSIONS: Supplementation of n-3 PUFAs is effective to relieve pain and improve joint function in patients with OA.

Nutrition and its role in prevention and management of rheumatoid arthritis.

Accumulating research evidence suggests that nutrition might be implicated in the risk of development and in the management of autoimmune disease, including rheumatoid arthritis (RA), characterized by immune-inflammatory response. Nutrition can have direct roles through the provision of pro- or anti-inflammatory foods, and indirect roles through management of co-morbidity management. The review updates on the evidence relating RA risk and management with focus on specific foods such as fish and diets/dietary patterns such as the Mediterranean diet, fasting and elimination diets and oral nutritional supplements including omega-3 polyunsaturated fatty acids (PUFA). Evidence on herbs and spices, beverages, Vitamin D, and probiotics is also reviewed. Diet has been shown to improve disease activity through reducing inflammation and oxidation and through its beneficial effects on the gut microbiota. Based on the existing evidence, it is recommended that as an adjunct to medical treatment, nutrition therapy for RA should be based on an anti-inflammatory Mediterranean diet (MD) supplemented with at least twice a week consumption of oily fish and/or omega-3 PUFA supplements at 2 g/day. The need for rheumatologists to work more closely with registered dietitians in the management of patients particularly in supporting a well-balanced diet according to individual needs, is highlighted.